P1518: INFECTIONS FOLLOWING BISPECIFIC ANTIBODIES IN MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Gemma Reynolds, Edward R Scheffer Cliff, Ghulam Rehman Mohyuddin, Rakesh Popat, Sholani Midha, Melissa Ng Liet Hing, Simon Harrison, Aaron Kesselheim, Benjamin W Teh
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Improved understand of infection risk amongst myeloma (MM) patients (pts) treated with bispecific antibodies (BsAbs) against plasma cell (PC) antigens BCMA, GPR5, FcRH5 is required. Aims: We conducted a systematic review and meta-analysis to evaluate infection rates amongst MM pts receiving BsAbs. Methods: A systematic literature search used Medline, Clinicaltrials.gov, Cochrane, Google Scholar, Embase, and major conference abstracts, with MeSH auto-exploded keywords for “multiple myeloma” AND “bispecific antibody” or “BiTE”. We included trials and abstracts published prior to Jan 26 2023 reporting infectious adverse events in English. Meta-analysis of proportions estimated pooled infection incidence using random effect models (Mantel-Haenszel) in R-4.2.2. Results: 799 studies were screened and 6 Phase 1 and 6 phase 2 clinical trials included (N = 1409 pts, median age 64.5 years). 52% of pts (95%CI: 44-59%) experienced an infection of any grade. 23% of patients (95%CI: 17-29%) experienced a Grade ≥ 3 infection. Severe infections were higher amongst BCMA-treated pts (N = 807, 27%, 95%CI: 19 – 35%), compared to GPRCD5-treated pts (N = 442, 18%, 95%CI: 12-23%), but did not differ for all-grade infections (52 vs. 53%). Grade ≥ 3 neutropenia occurred in 29% of pts. Summary/Conclusion: Despite promising efficacy in MM, BsAbs may come with substantial infection risk, warranting more detailed analysis of infections and immune phenotyping to guide targeted supportive care. Table – Summary of included studies - Agent Target Source Phase Enrolment(mm/yy) N Median prior lines All-Grade InfectionN (%) Grade ≥3 InfectionN (%) Grade 5 InfectionsN (%) Grade ≥3 CRSN (%) ORR % ≥VGPRR % Median DORmonths Median Follow-upmonths (Range) Alnuctamab (CC-93269) BCMA Wong 2022 I 03/18- 68 4 23 (34) 6 (9) 0 0 53 40 NR 4.1 ABBV-383 BCMA Voorhees 2022 I 10/22- 174 5 61/124 (50) 39/124 (22) 8/124 (6.5) 1 (0.5) 59 44 9 6.8 (0.9 – 33.7) Elranatamab BCMA Raje 2022 I 10/21- 123 5 82 (67) 43 (35) 6 (5) 0 61 55 17 10.4 (0.3-29) Linvoseltamab (REGN545) BCMA Bumma 2022 Ib/II 1/19- 252 5 136 (54) 73 (29) 10 (4) 2 (1) 57 42 NR 3.2 Pacanalotamab(AMG-420) BCMA Topp 2020 I 3/19 – 4/22 42 5 14 (33) 10 (24) 2 (5) 1 (2.4) 70 60 9 NR Teclistamab BCMA Moreau 2022 I/II 09/20- 165 5 126 (77) 57 (45) 12 (7) 1 (0.6) 63 55 18.4 14.1 Teclistamab + daratumumab BCMA + CD38 Rodriguez-Otero 2022 II 03/21- 46 5 29 (63) 8 (17) 0 0 78 73 Not reached 3.6 (0.1–10.4) Forimtamig (RG6234) GPRC5D Carlo-Stella 2022 I 11/20- IV: 51SC: 57 IV: 5SC: 4 IV: 31 (61)SC: 26 (46) IV:11 (22)SC:15 (27) IV: 1 (2)SC: 1 (2) IV: 1 (2)SC: 1 (1.9) IV: 71SC: 64 IV: 59SC: 53 IV: 10.8SC: 12.5 IV: 11.6SC: 8.0 Talquetamab GPRC5D Chari 2022 I/II 02/21- 288 5 153 (53) 46 (16) 2 (0.7) 2 (1.8) 73 58 0.4mg: 10.20.8mg: 7.8 0.4mg: 14.90.8mg: 8.6 Talquetamab + daratumumab GPRC5D + CD38 Van de Donk 2022 II 09/21- 46 5 23 (50) 6 (13) 0 0 77 65 Not reached NR Cevostamab(BFCR4350A) FcRH5 Trudel 2021 I 07/21- 161 6 68 (43) 18 (11) 0 2 (1) 90mg: 36160mg:57 90mg: 21160mg:33 90mg: 11.5160mg NR 90mg: 14.3160mg: 6.5 Keywords: Bispecific, Multiple myeloma, Cellular therapy